Table 2.

Classification of cryoglobulins and laboratory findings[4,18]

Cryoglobulin type	Content	Related diseases	Laboratory findings
Type I	Monoclonal immunoglobulins (IgG, IgM or IgA) or Bence Jones protein/monoclonal free light chains	Multiple Myeloma	Precipitation within 24 h Hyperviscosity
		Waldenstrom Macroglobulinemia
		Lymphoproliferative disease related monoclonal gammopathy
		Light chain disease
Type II (mixed)	Monoclonal immunoglobulins (IgG, IgM or IgA) and polyclonal immunoglobulins (usually IgG)	HCV	Precipitation within 7 d HCV positivity Decreased C3 Decreased C4 Decreased CH50 Increased autoantibodies such as ANA, ENA, AMA
		Essential cryoglobulinemia
		Sjogren’s syndrome
		Rheumatoid arthritis
		Chronic lymphocytic leukemia
Type III (mixed)	Polyclonal immunoglobulins	Essential cryoglobulinemia
		Sjogren’s syndrome
		Systemic lupus erythematosus
		Viral infections (HBV, CMV, EBV, HIV)
		Endocarditis
		Biliary cirrhosis

Type I cryoglobulin concentrations are > 5 g/L, so that they tend to precipitate within 1 d; whereas in mixed cryoglobulinemia, development of precipitation can take a couple of days[2]. After the precipitation is observed samples should be incubated at 37 °C again and dissolution of the precipitates at this temperature should be confirmed. If the precipitates do not dissolve at 37 °C, test should be reported to be negative. HBV: Hepatitis B virus; CMV: Cytomegalovirus; EBV: Epstein-Barr virus; ANA: Antinuclear antibodies; ENA: Extractable nuclear antigen antibodies; AMA: Antimitochondrial antibodies; HIV: Human immunodeficiency virus.